TW200831117A - Shiunko nanomicell for skin treatment and preparation method for the same - Google Patents

Shiunko nanomicell for skin treatment and preparation method for the same Download PDF

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TW200831117A
TW200831117A TW096103618A TW96103618A TW200831117A TW 200831117 A TW200831117 A TW 200831117A TW 096103618 A TW096103618 A TW 096103618A TW 96103618 A TW96103618 A TW 96103618A TW 200831117 A TW200831117 A TW 200831117A
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nano
extract
oil
package
comfrey
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TWI364288B (en
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Chih-Haoo Chang
Tong-Rong Tsai
Wen-Lung Hu
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Univ Kaohsiung Medical
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/30Boraginaceae (Borage family), e.g. comfrey, lungwort or forget-me-not
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/107Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02Local antiseptics

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Abstract

An improved nanomicell solution of Chinese traditional Shiunko oil is provided, which replace the sesame oil with olive oil and mineral oil as the solvent, and cover the oil particles thereof with hydrophilic layers by nanomicell technology, which make the oil particles as the nano-level particles. The improved nanomicell solution has the advantages of well skin infiltration and non-oily sensation, and excellent effects in bactericidal and wound healing abilities.

Description

200831117 九、發明說明: 【發明所屬之技術領域】 更特別關於一種 ^發明係關於一種紫雲膏製劑及製備方法 養雲言奈米微包製劑及製備方法。 【先前技術】200831117 IX. Description of the invention: [Technical field to which the invention pertains] More particularly relates to a method for preparing a purple cloud paste preparation and a preparation method thereof. [Prior Art]

紫ϊί為傳統帽製劑,主要《草、當歸、麻油及黃蝶所 s被II ,小々、…工文饵系平、^ ΐ呈有ίίΐΐ成ί包括紫草素及其衍生物,這-些成分已被證 二:f加速肉牙組織生長、縮短發炎時間、促進傷口癒合、Ziqi ί is a traditional cap preparation, mainly "grass, angelica, sesame oil and yellow butterfly s are II, small sputum, ... the work bait is flat, ^ ΐ is presented ίίΐΐ into ί including shikonin and its derivatives, this - Some ingredients have been proved: f accelerates the growth of meat tissue, shortens the time of inflammation, promotes wound healing,

Hi外用藥膏’價格便宜且製作容易。财溫下久置與^麻油味、油絲f料清洗為其常被提到的缺點 μ Ξ ΐί科界自1968祕,對於治療燒⑽病患卿含銀離-日龄%銨銀軟貧(S1lver sulfadiazinel%。作⑽)為主流,^ 疋以王個分子作用於細菌之細胞及細胞膜,引起細胞壁之變子 (deformation),損害細菌細胞膜之機能,來達到殺菌的目的 巧疋銀顆粒會沈澱在真皮層導致局部皮膚呈現藍灰色的外事 Argyria) ’甚至在單層培養(m〇n〇iayer cUhure)中被發天 到銀離子和sulfadiazine對角質細胞(keratin〇cytes)和翁 母細胞(fibroblasts)具有高度毒性會延遲癒合時間,同時銀袭 ^對細胞,毒,劑量和殺菌劑量相當接近,在殺菌的同時也容3 造成自體受到傷害,此外磺銨劑會抑制骨髓功能,磺銨類藥物^ 有過敏反應。 奈米彳数包液(Nanomicell)技術於近年被研發出,是高純度 磷脂質和溶劑(如甘油或丙二醇)的濃縮緣,能夠溶解油脂和一 般溫度下(25-60 °C)難溶于水的物質。用水稀釋該濃縮液會產 200831117 生呈封閉球形膜的微脂粒狀態及大小。奈米微包液是將脂溶性藥 巧覆於咖旨質之内,外層再裹以水層_成的透明濃縮液體, j穩定性佳、親水性高、生理安全、天輪刺激、*使用合成 的界面活性劑及防腐劑、不含乙醇、能提高活性物質的吸收和生 物利用率等優點。奈米級的顆粒大小的特性可經由細胞融合、内 包及吞噬作用而穿透細胞膜,是一種理想的藥物載體,可廣泛虡 /用,妝品、藥物製劑及生物醫學的研究。低於施m的奈来級粒 她皮吸收可快速達到真皮層’可從皮膚投藥以提供—非侵入性 且有效的給藥方式。 ,美國專利US6468553專利案件及台灣專利1226838專利荦件皆 冒對傳統紫雲膏的雌基質做過改良,然仍不脫油性基f所帶來 的^易清洗及使用不便關題,且相.吨術或許增加了傳统 i戶定性’然對於增加藥劑本身穿透皮膚或為患處組 、、我所吸收的此力卻無所助益。 有^於傳統餘膏及西醫含銀離子的外料銨銀軟膏之讎 =失’兔明人乃經細實驗與研究,並—核而不捨之精神,終 構思出本案,以下為本案之簡要說明。 【發明内容】 並 本發明以餘膏之喊藥物結合新穎奈米微包處理, 以撖欖油及礦物料不同錄基魏代麻作紫f 勺 及特殊味運:亚可進-步設計麟於敷藥及清洗的凝膠 =Hi topical ointment is cheap and easy to make. Long-term and low-cost with sesame oil, oily f material cleaning is often mentioned as the disadvantage of μ Ξ ΐί science from 1968 secret, for the treatment of burning (10) disease containing silver away - day age% ammonium silver soft (S1lver sulfadiazinel%. (10)) is the mainstream, ^ 疋 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王 王Precipitating in the dermis layer causes local skin to appear blue-gray foreign affairs Argyria) 'Even in monolayer culture (m〇n〇iayer cUhure), it is sent to silver ions and sulfadiazine to keratinocytes (keratin〇cytes) and engorgia cells ( Fibroblasts) are highly toxic and delay the healing time. At the same time, the silver attack is quite close to the cells, toxicity, dose and bactericidal dose. It also causes autologous damage during sterilization. In addition, the sulfonamide inhibits bone marrow function. Drugs ^ have an allergic reaction. Nanomicell technology has been developed in recent years. It is a concentrated edge of high-purity phospholipids and solvents (such as glycerin or propylene glycol), which can dissolve oil and is insoluble in normal temperature (25-60 °C). The substance of water. Dilution of the concentrate with water yields the state and size of the vesicles of the closed spherical membrane produced in 200831117. Nano microencapsulation is a kind of transparent soluble liquid which is made by coating a fat-soluble drug into the essence of the coffee. The outer layer is further wrapped with a water layer. The stability is good, the hydrophilicity is high, the physiological safety, the sky wheel stimulation, * use Synthetic surfactants and preservatives, no ethanol, can improve the absorption of active substances and bioavailability. Nano-sized particle size can penetrate cell membranes through cell fusion, inclusion and phagocytosis. It is an ideal drug carrier for a wide range of applications, cosmetics, pharmaceutical preparations and biomedical research. Below the application of the nano-grain, her skin absorption can quickly reach the dermis layer, which can be administered from the skin to provide a non-invasive and effective means of administration. The US patent US6468553 patent case and the Taiwan patent 1226838 patent case all have improved the female matrix of the traditional Ziyun cream, but still do not take off the oily base f. Easy to clean and inconvenient to use, and the phase. The surgery may increase the traditional i-finalization. However, it does not help to increase the penetration of the drug itself into the skin or the affected group. There are ^ traditional sugar paste and Western medicine containing silver ion of the external material ammonium silver ointment = lost 'rabbit Ming people through careful experiment and research, and the spirit of perseverance, the final idea of the case, the following is the case A brief description. SUMMARY OF THE INVENTION The present invention combines the treatment of the scent of the ointment with the novel nano-micro-package, and the different recordings of the eucalyptus oil and the mineral material, the Wei-Mao purple f spoon and the special taste transport: Ya Kejin-step design Gel for application and cleaning =

,減少燒气瘢痕增姻益處,得到—療效優 磺銨銀軟貧的紫雲膏奈米微包製劑。 U 人右人ii構想’提出—種治療皮膚病之奈米微包液, 3有下列成/7 .油性基質’―紫草萃取液以及—當歸萃取液, 200831117 其中該紫草萃取液及該當歸萃取液係利用該油性基質萃取紫草及 當歸而得。該油性基質、該紫草萃取液及該當歸萃取液則包覆於 一磷脂質(phospholipids)層内,形成粒徑小於1〇〇奈米之一本半 微包。 不 較佳者,該油性基質包含麻油、礦物油及橄欖油之至少其中 之一。 /、 較佳者,該奈米微包外更包覆一水層。 較佳者’該麟脂質層係由甘油及構脂質所組成。 較佳者,該皮膚病包括:跌打損傷、擦傷、刀傷、燒费傷、 皮膚乾燥、皸裂、潰瘍、凍傷及增殖性皮膚異常。 羽根據發明人另一構想,提出一種治療皮膚病之奈米微包凝 膠,其含有下列成分:一油性基質、一紫草萃取液、一當歸萃取 液^二賦形劑,其中該紫草萃取液及該當歸萃取液係利用該油性 萃取紫草及當歸而得。而該油性基質、該紫草萃取液及該當 歸萃取液則包覆於一麟脂質(phospholipids)層内,形成粒徑小於 100奈米之奈米微包。 、 較佳者,該賦形劑為一凝膠和一親水性軟膏其中之一。 較仏者,该油性基質包含麻油、礦物油及撖欖油之至少其中 之'~ 0 較佳者,該奈米微包外更包覆一水層。 較佳者,該磷脂質層係由甘油及磷脂質所組成。 根據發明人又-構想,提自-雜備治療皮編之奈米微包 /文的方法’其步驟包括:(a)利用一油性基質萃取一紫草與一舍歸 =得到一萃取液,(b)在該萃取液中加入一磷脂質及水/高速^壓 攪拌使該萃取液均質化,(C)過濾該萃取液。 杈佳者,步驟(a)之前更包括一步驟:該當歸於室溫下先浸泡 於該油性基質中24小時。 200831117 較佳者,步驟(a)中更包括一步 130〜140度以萃取該紫草及該當歸。·係將該油性物質加熱至 較佳者,步驟(c)係使用濾徑〇 鲈杜|八、 _ M下的過濾膜而進行。 礦物油及橄欖油之 車乂佺者,步知(a)之該油性基質包 至少其中之一。 麻油、 •加入一賦形劑於過濾後 較佳者,步驟(c)之後更包含_步 的該萃取液並混和攪拌。 紛圭者,該賦形劑為—凝膠及—親水性軟膏其中之一。 藉由上述製備方法及脂溶性筚铷 但藥物對皮膚的穿透力可以提升的奈米化和親水化,不 統油性基質不易清洗與保存不易的問同時傳 確實的瞭解。 亚配β圖示之參閱而的到 實施方式】 路—種紫雲t奈米微包製劑及製備方法,其内容將 二由15施例說明如下,然該等實施例僅為其中較佳者 ,本發 #始二也亚非僅!^於該等較佳實施例,熟習同領域技術人士仍可 既揭露之貫施例的精神推演出其他實施例,該等實施 當屬於本發明之範圍。 在本員驗中所使用之紫草為軟紫草(即新疆紫草Arnebia e^cpronia) ’ 所用富 |听係指 Angelica sinensis (01 iv· ) Diels 的 乾,根。首先說明本發明不同紫雲膏製劑實施例之製備方法,再 以實驗測試說明本發明優於習知技術之功效: 實施例: 200831117 中藥材製作不同油性基皙 S組··紫草90 .公克、當歸90公克、麻油300公克。 〇組·紫草9〇公克、當歸90公克、橄欖油3〇〇公克。 Μ組:紫草9〇公克、當歸90公克、礦物油3⑽公克。 先將當歸棟淨雜質,室溫下置油中浸24小時後,在電磁爐上 加熱至130-140°C當歸顏色呈焦枯為度,最後加入揀淨雜質的紫 草’溫度持續維持在130-140 °C15分鐘,見紫草脆而易折斷,油 液變為紫紅色,再從電磁爐上移開,用构子撈除當歸和紫草,趁 熱將油液用消毒後的4層紗布過濾,濾液倒入玻璃瓶中貼標籤備 用。 例(二)紫雲膏奈米徽包液之 材料:(1)實施例一之S、0、M組成品 (2) 甘油 (3) Phospholipid (4) 純水 方法:-^Phospholipid加入(1)中授拌 —前步驟混合液倒入甘油中攪拌 —純水加入前步驟混合液中 —高速乳化均質機高速攪拌 —倒入高壓均質機均質化 —0.1/zm過濾膜過濾 一收集紫色濃縮液 200831117 膏奈来饊釔凝膠之製備方法 摔,紫雲f奈米微包液100cc+透明凝简混合授 功效測試實驗:To reduce the benefits of burning scars and increase the benefits of marriage, and to obtain a high-efficiency sulfonium-silver-purple purple cloud cream nano-package preparation. U Renyou ii conceived 'proposed to treat nano skin microencapsulation for skin diseases, 3 has the following formation /7. Oily substrate' - comfrey extract and - Angelica extract, 200831117 where the comfrey extract and the The extract of Angelica sinensis is obtained by extracting comfrey and angelica using the oily substrate. The oily substrate, the comfrey extract and the angelica extract are coated in a phospholipids layer to form a semi-microcapsule having a particle size of less than 1 nanometer. Preferably, the oily base comprises at least one of sesame oil, mineral oil and olive oil. /, preferably, the nano-micro package is coated with a water layer. Preferably, the lining lipid layer consists of glycerol and a constitutive lipid. Preferably, the skin condition comprises: bruises, abrasions, cuts, burns, dry skin, chapped, ulcers, frostbite and proliferative skin abnormalities. According to another concept of the inventor, a nano-package gel for treating skin diseases is proposed, which comprises the following components: an oily substrate, a comfrey extract, an angelica extract, and an excipient, wherein the comfrey The extract and the Angelica extract are obtained by extracting the comfrey and angelica with the oily extract. The oily substrate, the comfrey extract and the extract of the extract are coated in a layer of phospholipids to form a nano-package having a particle size of less than 100 nm. Preferably, the excipient is one of a gel and a hydrophilic ointment. More preferably, the oily base comprises at least one of sesame oil, mineral oil and eucalyptus oil, and the outer layer of the nano-package is coated with an aqueous layer. Preferably, the phospholipid layer is composed of glycerin and phospholipids. According to the inventors' conception, the method of extracting from the nano-package/texture of the skin preparation process comprises the steps of: (a) extracting a comfrey with an oily substrate and obtaining an extract; (b) The extract is homogenized by adding a phospholipid and water/high speed stirring to the extract, and (C) filtering the extract. Preferably, step (a) further comprises a step of: immersing in the oily substrate for 24 hours at room temperature. 200831117 Preferably, step (a) further comprises a step of 130 to 140 degrees to extract the comfrey and the angelica. The heating of the oily substance is preferably carried out, and the step (c) is carried out using a filtration membrane of the filtration membrane 八 | | 八 八 _ _ M. For the ruts of mineral oil and olive oil, at least one of the oily base packs of step (a). Sesame oil, • It is preferred to add an excipient after filtration, and further, after step (c), the extract is further mixed and stirred. In some cases, the excipient is one of a gel and a hydrophilic ointment. By the above-mentioned preparation method and fat-soluble hydrazine, the penetrating power of the drug on the skin can be improved by the nanocrystallization and the hydrophilization, and it is difficult to clean and save the hard-to-oil substrate. Reference to the embodiment of the sub-β, the embodiment of the method of the invention, the method of preparing the micro-package and the preparation method of the method, and the content thereof will be described by the following 15 examples, but the examples are only preferred. This issue #始二也亚非only! In the preferred embodiments, those skilled in the art will be able to devise other embodiments in the spirit of the invention, which is within the scope of the invention. The comfrey used in our test is the soft comfrey (ie, Arnebia e^cpronia) used by the 'sweetness of the Angelica sinensis (01 iv· ) Diels. First, the preparation method of the different purple cloud paste preparation examples of the present invention will be described, and the effects of the present invention over the prior art will be demonstrated by experimental tests. Example: 200831117 Chinese herbal medicines are prepared with different oily bases, group S·· comfrey 90. Angelica 90 grams, sesame oil 300 grams. 〇 group · comfrey 9 〇 grams, angelica 90 grams, olive oil 3 〇〇 grams. Μ group: comfrey 9 gram grams, angelica 90 grams, mineral oil 3 (10) grams. First, the net impurities of Angelica sinensis were immersed in oil for 24 hours at room temperature, and then heated to 130-140 °C in the induction cooker. The color of the angelica was scorched, and the temperature of the comfrey that was added to the impurities was maintained at 130- At 140 °C for 15 minutes, see the comfrey crisp and easy to break, the oil turns purple, then remove from the induction cooker, remove the angelica and comfrey with the structure, filter the oil with the disinfected 4 layers of gauze. The filtrate is poured into a glass bottle and labeled for use. Example (2) Material of Ziyun cream nano-enveloping liquid: (1) S, 0, M components of Example 1 (2) Glycerin (3) Phospholipid (4) Pure water method: -^Phospholipid added (1) Middle-mixing - pre-step mixture is poured into glycerin and stirred - pure water is added before the mixing step - high-speed emulsification homogenizer high-speed stirring - pouring into high-pressure homogenizer homogenization - 0.1 / zm filter membrane filtration - collecting purple concentrate 200831117 The preparation method of the cream Neil 饊钇 gel falls, Ziyun f nano-package liquid 100cc + transparent condensed simple mixed effect test experiment:

粒徑分析實驗 儀裔· Beckman coulter TM N5粒徑分析儀 方法·—滴,待測樣品—小滴,滴人裝有⑽W的二次水燒 杯中,搖盪均勻。 —上液取2-3滴滴入已裝有二次水的透明cell内 —置入粒徑分析儀内之正確位置 2動軟II檢測,每讎品均測量三次取其平均值做紀 錄。 結果:速處理製備所得麻油紫草奈米福 測1粒^ 麵包液、鶴油紫草奈米微包液名 為紫雲;奈;微二理成第-圖’ 後粒徑可達到小於刚抽經奈米微包技術處至 天,絲徑大水準。於室溫下放置15 方法:分成不含藥的對照組、藥 古杜 :tr;草包; 種菌種為抑菌試驗以=二τ内感含= 200831117 的總菌數)的各菌種置入各含有上述六 Soy Broth玻璃瓶中授拌,於阶下培養: ®^^35Ϊ: 馬血/爷木培養基(H〇rse B1〇〇(1 A ) 小時,觀察細菌生長情形並計算菌落^。ubcult㈣24 結果: 各菌種測試結果分列於表3至表7,同時請參 (A)(B),其為pseud〇monasae_ 菌(峥 '弟一圖 驗⑹、市^(:===== 、、且⑴各培養0、8及24小時候菌落圖; 、、 Ί、ϊίΐϊίΐΐ^σ或化膿組織最常被培養出的菌種,易 ^囷,症甚至¥致燒费傷病患的死亡。於確 實可抑制綠膿桿菌。 王貝不心明確 ()Pseudomonas aeruginosa 如表3所示: 1、於〇分鐘菌落數>1〇5個、8小時菌落數〇個、2“、 守菌洛數0個’顯示對pseud〇monas aerugin〇sa菌抑制效 極佳。 ^ 2、 3、 市售π口紫雲霄對pseud〇monas aerUgjnoSa菌無抑菌作用。 麻油紫草奈米微包液於〇分鐘菌落數>105個、8小時菌落數丨 1 固24小日守囟落數〇個’顯示對pseud〇m〇nas erUgin〇sa 抑制效果極佳。 j敢欖油紫草奈米微包液於〇分鐘菌落數>1〇5個,8小時菌落索 個、24小時囷落數0個,顯示對pseu(|omonas aerUgin〇sa 菌抑制效果極佳。 4、 200831117 丨示對Pseudomonas aeruginosa 鐘菌落數…個,8小時菌落數 囷抑制效果極佳。 (二)Escherichia coli 如表4所示: 1、磺銨銀對Escherichia coli菌抑制效果極佳。 • 2、市售品紫雲膏對Escherichiac〇lig無抑菌作用。 3、=紫草絲微包液、橄欖油紫草奈米微包液、刺 奈米微包液對Escherichia coli菌無抑制效果。'、务、卓 (^) Enterococcus faecal is 如表5所示: 1、 磺銨銀對Enterococcus faecal is菌抑制效果極^土 2、 市售品紫雲膏對Enterococcus faecalis菌無抑菌作用。 • 3、麻油紫草奈米微包液、橄欖油紫草奈米微包液、。 奈米微包液對Enterococcus faecalis菌無抑制由紫草 (四)Proteus mirabilis 如表6所不. 1、 石黃銨銀對Proteus mirabilis菌抑制效果極佳。 2、 市售品紫雲膏對Proteus mirabilis菌無抑菌作用 3、 麻油紫草奈米微包液、橄欖油紫草奈米微包、、存 。狀、碾物油紫草 12 200831117 奈米微包液對Proteus mirabilis菌無抑制效果。 (五)Acinetobacter baumannii 如表7所示: 1、 石黃敍銀對Acinetobacter baumannii菌抑制效果極佳。 2、 市售品紫雲膏對Acinetobacter baumannii菌無抑菌作用。 3、 麻油紫草奈米微包液、撖欖油紫草奈米微包液、礦物油紫草 奈米微包液對Acinetobacter baumannii菌抑制效果不^圭。 政效測試實驗(三)燒燙傷瘓效之評仕 實驗動物]12隻兔子(雄性紐西蘭家兔,New Zealand 方法及步驟:(减雄醫學大學醫研大樓實驗動物中心進行)_ (1)燒燙傷模型建立 1、 實驗開始前,先將兔子用不含殺菌藥物之肥矣清 Μ 使用電剪將兔子背部剃毛。 先待毛乾後 2、 ketamine 40mg/kg之劑量肌肉注射麻醉。 3、 將12隻兔,分成6組(A、B兔為第一組,C、D 一 H兔么第、三組,_!、H兔為第四組,丨、·1兔為第五紅了κ且ί 兔為弟六、,且),同-組兔子於褒傷後所敷藥物部位相同。 知方向改變位置依序敷上實驗用之外用藥膏 =、1叫 sulfadiazinel% cream、市售势录良二丄此 ’、、、、、’ Sllver 勝、橄㈣紫雲膏奈米微包凝膠 200831117 ^〇·5公克)’用防水透氣透明膠布(TegadermTM)覆蓋於藥 膏之上。 ’、 5、 待清醒後放回動物實驗中心飼養籠内,於室溫下以正常兔 食飼養。 6、 術後每天敷藥並拍照,第3〇天以後每兩天敷藥一次並拍照至 傷口完全癒合。 7、 為防止兔子舔食傷口上藥物而影響療效觀察評估,每次於換藥 後將兔子戴上自行設計之頸罩。 ⑩8、/實驗進行後第5、10、15、2〇、25及3〇天各取一隻兔子犧牲 後’以手術剪取下各創傷面皮膚放置於10%福馬林溶液中送病 理科做切片請病理科專科醫師協助觀察組織學變化。 9、其餘6隻兔子共36個創面繼續敷藥至傷口癒合並觀察疤痕攣縮 情形。 (2)病理切片 將兔子犧牲後取下各創面皮膚,約3 X 3cm的面積固定於1〇% ⑩福馬林溶液中,經脫水、脫脂、包埋,用切片機切成3〜6//m的厚 度’固定於玻片上,經Η & e (Hematoxylin & Eosin)染色後以 顯微鏡觀察。依Hyperkeratosis (表皮過度角化程度)、Epidermal hyperplasia(表皮增生程度)、Hair foilicles(毛囊)、Apocrine glands(大汗腺)、Smooth muscles (平滑肌)、Fibroplasia (纖 維母細胞增生程度)、Vascular pr〇Hferati〇rl (新生血管增生 程度)'Collagen orientation (膠原組織生長程度)等顯微鏡 下組織結構變化來評估燙傷後瘢痕生長情形及傷口攣縮預後好 壞,給予評分(Adam J· Singer et al·,2000)。 14 200831117 έ士要· ν'σ * (一)傷口外觀癒合程度評估 兔子傷口外觀癒合程度評估,依傷口外觀給予以 ^、 ^ :雙痂已脫落,傷口已癒合,瘉人虛 之评分· «哽已脫落,傷π已癒合 售痂已脫落,傷口未癒合。〜处凸起。 傷口已結‘,無滲出液。 傷口部分結‘,有滲出液。 於爱傷後第31天及第37天做評分,總分越高者 評分結果請分別參閱表8及表9,同時參閱第三 ^麋放越佺。 別為第31天㈣取實驗_κ兔的傷σ外^^。分 和第37天以奈米微包凝膠塗敷的傷口癒合能力均優於^^細天 分 分 分 分 分 錢銀及市售 組 石黃 膠與 且以第37天評估,橄欖油紫雲膏奈米 礦物油紫,奈級包凝膠的促進傷口癒合能力相‘略j =紫雲t奈米微包凝膠。癒合後的傷口平坦 ^: 貧奈米微包凝膠較佳。 η見/由1¾ 其次,市售品紫雲膏以黃蠟為基劑,塗敷在傷口上 清洗、換藥時傷口似乎特別敏感疼痛(由兔子極力掙扎可知)为 _ 皮膚及兔毛染成紫紅色後不易褪除,影響外表美觀等缺點。但這 些現象均於使用撖欖油紫雲膏奈米微包凝膠與礦物油紫带暮太^ 微包凝膠的傷口處獲得改善。 农 (二)病理學變化 表11為其中一隻實驗動物傷口燒燙傷後第五天的病理切片評 分紀錄表,評分等級從最壞的〇分到最接近正常皮膚的1〇分不等。 並分別於燒燙傷後的第10天、第15天、第20天、第25天、第30天 紀錄之’總表結果整理如表1〇,同時請參閱第5圖(A)_(F),其分 別為燒燙傷後第20天對照組、磺銨銀組、市售品組、SSN組、0SN 組及MSN組於光學倍數2〇倍下傷口組織的H&E染色圖。由表1〇及組 15 20083ι117 織染色圖的結果可知: 1.於第5天的組織切片評分表裡,六種敷料中有五種 〜20、25、30天還要好’可翻為剛魏的喊血 去 ^被被鑛’ _皮膚組_能財部絲魏前的結^^ 微 2.以齡評估六錄料之傷鴻合及瘢痕_ 太 包破膠的三組都優於對照組、磺銨銀組與市售品。 不未 技3.奈米微包凝膠組内比較發現礦物 油㈣膏奈米微包凝膠其次,麻油紫 綜上所述,可知本發明所製成的3種麻油視物 =奈米微包液,於室溫下放侧天後仍能保持小於廣 囷具有極佳的抑s能力4於紫雲f奈米微包凝 叙銀軟賞。此外創面易於清洗、癒合不紫 皆是本發明之-大進步功效。械~ 4、色於毛皮上 ^紐西闌減t傷模贿察得知橄欖 破 :物油紫雲膏奈米微包凝膠的促進傷口齋合 坦程度以橄禮油紫雲膏奈米微包凝膠瘢痕平 發現以礦物油紫雲膏奈米微包凝膠復精 2估結果則 其次,麻油紫料奈 #為說明本發日狀顧及其功效,__本發明。 微包雜的三、_優於舰組、频銀組與市錢草膏。於不未 16 200831117 ‘· 技術之人士可在不本發明之精神對上述實施例進行修改及變 化。本發明之權利範圍應如後附之申請專利範圍所列。 • 參考文獻: 1. Adam J. Singer, Henry C. Thode Jr.5 Steve A. McClain. Development of a histomorphologic scale to quantify cutaneous scars after burns. Acad Emerg Med. 2000,7(10):1083-1088 17 200831117 圖表說明: 表1粒徑資料表 麻油紫雲貧 奈米微包液 橄欖油紫雲膏 奈米微包液 礦物油紫雲膏 奈米微:包液 第01天 66. 6±25. 8 nm 80· 5土25· 5 nm 70. 8±27. 7 nm 第20天 99. 0+31. 6 nm 79.1±25. 0 nm 44. 7+20. 4 nm 第30天 78. 7±27· 5 nm 91. 2+30. 5 nm 75. 8±26. 7 nm 第40天 71·9±22.4 nm 78. 3+23. 4 nm 80.1+24. 6 nm 第50天 76. 2+22. 7 nm 80. 7±26. 9 nm 92. 9±31.2 nm 第60天 73· 4±29· 4 nm 90· 2土30· 9 nm 66. 4+23. 2 nm 第150天 86·9±40·9 nm 89.1+28. 8 nm 84. 0±24, 6 nm 表2本貫驗抑囷對象的五種菌種! 聲 抑菌對象 菌種編號 Pseudomonas aerug i nosa (綠膿桿菌) NCTC 10662 Escherichia coli (大腸桿菌) ATCC 35218 Enterococcus faecal is (糞腸球菌) ATCC 29212 Proteus rairabilis (變形桿菌) ATCC 7002 Acinetobacter baumannii (鮑氏不動桿菌) ATCC 19606 18 200831117Particle size analysis experiment Instrumentary · Beckman coulter TM N5 particle size analyzer Method · Drop, sample to be tested - droplets, drip in a (10) W secondary water beaker, shake evenly. - Take 2-3 drops of the upper liquid into the transparent cell containing the secondary water - place it in the correct position in the particle size analyzer. 2 Check the dynamic soft II and measure the average value of each product for three times. RESULTS: The sesame oil was obtained by the rapid treatment. The grain of the sesame oil was measured. The bread liquid and the oily liquid of the sylvestre sylvestris were named as Ziyun; Nai; the micro-two physics into the first-graph 'the particle size can be less than just pumping. Through the nano-micro-package technology to the sky, the wire diameter is high. Placed at room temperature 15 Method: divided into no drug-containing control group, drug Gudu: tr; grass bag; seed strain is bacteriostatic test = = 2 τ inner sensation = total number of bacteria in 200831117) Into each of the above six Soy Broth glass bottles, mix and culture under the order: ®^^35Ϊ: Horse blood/woodwood medium (H〇rse B1〇〇(1 A) hours, observe bacterial growth and calculate colonies^ Ubcult (4) 24 Results: The test results of each strain are listed in Tables 3 to 7, and please refer to (A) (B), which is pseud〇monasae_ bacteria (峥's one picture test (6), city ^ (:=== == , , and (1) colony maps for 0, 8 and 24 hours of culture, respectively; , , Ί, ϊ ΐϊ ΐϊ ΐΐ 或 or purulent tissues are the most commonly cultivated strains, easy to sputum, disease and even ¥ to burn the injured patients Death. It can indeed inhibit Pseudomonas aeruginosa. Wang Bei is not clear () Pseudomonas aeruginosa as shown in Table 3: 1, the number of colonies in the minute &; 1 〇 5, 8 hours of colonies 〇, 2 ", 守The number of bacteria is 0, which shows excellent inhibition against pseud〇monas aerugin〇sa. ^ 2, 3. Commercially available π mouth Astragalus membranaceus has no antibacterial activity against pseud〇monas aerUgjnoSa Use. The number of colonies of sesame oil lycopene micro-encapsulated liquid in 〇 minute > 105, the number of colonies in 8 hours 丨 1 solid 24 small days, the number of stagnations 〇 one 'shows the effect of pseud〇m〇nas erUgin〇sa j. The number of colonies of j. sylvestris sylvestris var. chinensis microcapsules in 〇; 1 〇 5, 8 hours of colony, 0 number of 24 hours, showing inhibition of pseu (|omonas aerUgin〇sa 4, 200831117 The number of colonies of Pseudomonas aeruginosa is very good, and the effect of 8 hours of colony is excellent. (2) Escherichia coli is shown in Table 4: 1. Inhibition effect of sulfonium silver on Escherichia coli Excellent 2. • 2. The commercially available Ziyun cream has no antibacterial effect on Escherichiac lig. 3. 紫草丝微包液, olive oil 紫草奈米微包液, 刺奈米微包液 to Escherichia coli No inhibition effect. ', service, Zhuo (^) Enterococcus faecal is as shown in Table 5: 1, sulfonium silver inhibits Enterococcus faecal is extremely effective soil 2, the commercial product Ziyun cream is not bacteriostatic to Enterococcus faecalis 3. 3, sesame oil licorice micro-package, olive oil lavender nano-micro The liquid encapsulation, nano-encapsulation of Enterococcus faecalis is not inhibited by comfrey (4) Proteus mirabilis as shown in Table 6. 1. The inhibitory effect of pyrophyllin silver on Proteus mirabilis is excellent. 2. The commercially available product Ziyun cream has no antibacterial effect on Proteus mirabilis. 3. The sesame oil lycopene micro-encapsulation solution, olive oil lavender nano-package, and storage. Shape, milled oil comfrey 12 200831117 Nano microencapsulation has no inhibitory effect on Proteus mirabilis. (5) Acinetobacter baumannii as shown in Table 7: 1. Shihuangxue silver has excellent inhibitory effect on Acinetobacter baumannii. 2. The commercially available Ziyun cream has no antibacterial effect on Acinetobacter baumannii. 3, sesame oil lycopene micro-encapsulated liquid, eucalyptus oil licorice nano-package liquid, mineral oil comfrey nano-encapsulation effect on Acinetobacter baumannii bacteria is not ^. Political test (3) Burning burns and effective evaluation of experimental animals] 12 rabbits (male New Zealand rabbits, New Zealand methods and procedures: (Attenuation Medical Laboratory Building Experimental Animal Center) _ (1 The establishment of a burn-and-burn model 1. Before the start of the experiment, the rabbits were cleaned with a non-bacterial drug. The back of the rabbit was shaved with an electric scissors. After the hair was dried, the ketamine 40 mg/kg dose was anesthetized. 3, 12 rabbits, divided into 6 groups (A, B rabbits for the first group, C, D a H rabbits, the third group, _!, H rabbit for the fourth group, 丨, · 1 rabbit for the fifth Red κ and ί rabbits are the younger brothers, and), the same group of rabbits applied the same drug parts after the bruises. The direction of change of the direction is applied to the experimental external use ointment =, 1 called sulfadiazinel% cream, city The sales volume is good for this two, ',,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, ‘, 5, after waking up, put it back into the cage of the animal experiment center and raise it at normal room temperature at room temperature. 6. Apply and take photos every day after surgery. Apply once every two days after the third day and take photos until the wound is completely healed. 7. In order to prevent the rabbit from ingesting the drug on the wound and affecting the observation and evaluation of the therapeutic effect, the rabbit is put on the neck cover designed by the rabbit after the dressing change. 108, / After the experiment, 5, 10, 15, 2, 25, and 3 days, each rabbit was sacrificed. 'Surgical scissors were taken and placed in 10% formalin solution for pathology. Slice the pathology specialist to assist in observing histological changes. 9. A total of 36 wounds from the remaining 6 rabbits continued to be applied to the wound healing and observed for scar contracture. (2) Pathological section The rabbits were sacrificed and the skin of each wound was removed. The area of about 3 X 3 cm was fixed in 1%% 10 marinine solution, dehydrated, degreased, embedded, and cut into 3~6// with a microtome. The thickness of m was fixed on a glass slide and stained with 显微镜 & e (Hematoxylin & Eosin) and observed under a microscope. According to Hyperkeratosis, epidermal hyperplasia, Hair pigmentation, hair follicles, Apocrine glands, Smooth muscles, Fibroplasia, Vascular pr〇Hferati 〇rl (degree of neovascularization) 'Collagen orientation' and other changes in tissue structure under the microscope to assess the scar growth after burn and the prognosis of wound contracture, scored (Adam J. Singer et al, 2000) . 14 200831117 Gentleman wants · ν'σ * (1) Assessment of the appearance of wound healing The evaluation of the healing degree of the wound in rabbits is given according to the appearance of the wound. ^, ^ : The sputum has fallen off, the wound has healed, and the score of the person is imaginary. The cockroach has fallen off, the wound π has healed and the sputum has fallen off, and the wound has not healed. ~ Raised at the place. The wound has been knotted ‘, no exudate. The wound partially knots ‘, there is exudate. On the 31st and 37th day after the injury, the score is higher. The higher the total score, please refer to Table 8 and Table 9, respectively, and refer to the third ^麋放佺. Don't take the experiment _κ rabbit's injury σ outside ^^ for the 31st day (4). On the 37th day, the healing ability of the wound coated with nano-microgel was better than that of the fine-grained silver and the commercially available group of yellow gum and evaluated on the 37th day. Paste nano-mineral oil purple, Nai-grade gel to promote wound healing ability 'slightly j = Ziyun t nano-package gel. The wound after healing is flat ^: The nano-package gel is preferred. η见/由13⁄4 Secondly, the commercial product Ziyun cream is based on yellow wax, applied to the wound for cleaning, and the wound seems to be particularly sensitive to pain when changing the dressing (known by the rabbit). _ Skin and rabbit hair dyed purple After the hard to fade, affecting the appearance of appearance and other shortcomings. However, these phenomena were all improved in the wounds using the eucalyptus oil violet cream nano-package gel and the mineral oil purple ribbon 暮 too ^ micro-gel gel. Agriculture (2) Pathological changes Table 11 shows the pathological scores of the fifth day after burn wounds in one of the experimental animals. The scores ranged from the worst scores to the nearest one. And the results of the 'Total Tables' recorded on the 10th, 15th, 20th, 25th, and 30th days after burns are listed in Table 1〇, and also refer to Figure 5(A)_(F ), which are the H&E staining maps of the wound tissue at the optical magnification of 2〇 times in the control group, the sulfonium silver group, the commercial product group, the SSN group, the 0SN group, and the MSN group on the 20th day after the burn. From the results of the staining diagrams in Table 1〇 and Group 15 20083ι117, we can see that: 1. In the tissue section score table on the 5th day, there are five kinds of six dressings ~20, 25, 30 days, even better. The screaming blood goes to the quilt's _ skin group _ can the Ministry of Finance and the silk before the end of the ^ ^ micro 2. Age-receiving six records of the wounds and scars _ Taibao broken three groups are better than the control group , sulfonium silver group and commercial products. No. 3. Nano-micro-gel group found in the mineral oil (four) cream nano-package gel followed by sesame oil purple in summary, we can see that the three kinds of sesame oil produced by the invention = nano micro The liquid encapsulation can still be kept below the vast area after being placed at room temperature for a long time. It has excellent s-suppressing ability 4 in Ziyun f nano-packaged silver soft reward. In addition, the wound is easy to clean and the healing is not purple. ~~~~~~~~~~~~~~~~~~~~~~~~~~~^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ The gel scar was found to be the result of mineral oil Ziyun cream nano-microgel gel re-extraction 2, followed by sesame oil-purple nai # to illustrate the hair and its efficacy, __ the present invention. The micro-packaged three, _ is better than the ship group, the frequency silver group and the city money grass paste. The above embodiments may be modified and changed without departing from the spirit of the present invention. The scope of the invention should be as set forth in the appended claims. • References: 1. Adam J. Singer, Henry C. Thode Jr. 5 Steve A. McClain. Development of a histomorphologic scale to quantify cutaneous scars after burns. Acad Emerg Med. 2000,7(10):1083-1088 17 200831117 Chart description: Table 1 Particle size data table sesame oil Ziyun lean nano-package liquid olive oil Ziyun cream nano micro-package mineral oil Ziyun cream nano-micro: liquid on the 01st day 66. 6±25. 8 nm 80· 5土25· 5 nm 70. 8±27. 7 nm Day 20 99. 0+31. 6 nm 79.1±25. 0 nm 44. 7+20. 4 nm Day 30 78. 7±27· 5 nm 91. 2+30. 5 nm 75. 8±26. 7 nm Day 40 71·9±22.4 nm 78. 3+23. 4 nm 80.1+24. 6 nm Day 50 76. 2+22. 7 nm 80. 7±26. 9 nm 92. 9±31.2 nm Day 60 73· 4±29· 4 nm 90· 2 soil 30· 9 nm 66. 4+23. 2 nm Day 150 86·9±40· 9 nm 89.1+28. 8 nm 84. 0±24, 6 nm Table 2 is the five species of bacteria that are tested and suppressed! Pseudomonas species No. Pseudomonas aerug i nosa (Pseudomonas aeruginosa) NCTC 10662 Escherichia coli (Escherichia coli) ATCC 35218 Enterococcus faecal is (Enterococcus faecalis) ATCC 29212 Proteus rairabilis (Proteus) ATCC 7002 Acinetobacter baumannii Bacillus) ATCC 19606 18 200831117

表3 NCTC 10662 Pseudomonas aeruginosa 菌落數 對照組 磺敍銀 市售品 SSN 0SN MSN 0分鐘 > I05 > 105 > 105 > I05 > 105 > 105 8小時 > 105 0 > 105 5 10 26 24小時 > 105 0 > ίο5 0 0 0 表4 ATCC 35218 Escherichia coli 菌落數 對照組 石黃錢銀 市售品 SSN 0SN MSN 0分鐘 > 105 > 105 > 105 > 105 > 105 > 105 8小時 > 105 0 > 105 > 105 > 105 > 105 24小時 > 105 0 > 105 > 105 > 105 > 105 表5 ATCC 29212 Enterococcus faecal is 菌落數 對照組 石黃錢銀 市售品 SSN 0SN MSN 0分鐘 > 105 > 105 > 105 > 105 > 105 > 105 8小時 > 105 0 > 105 > 105 > 105 > 105 24小時 > 105 0 > 105 > 105 > 105 > 105Table 3 NCTC 10662 Pseudomonas aeruginosa Colony number control group Sulfide silver commercial product SSN 0SN MSN 0 minutes > I05 > 105 > 105 > I05 > 105 > 105 8 hours > 105 0 > 105 5 10 26 24 hours> 105 0 > ίο5 0 0 0 Table 4 ATCC 35218 Escherichia coli Colony number control group Shihuang Qianyin commercial item SSN 0SN MSN 0 minutes> 105 > 105 > 105 > 105 > 105 > 105 8 hours > 105 0 > 105 > 105 > 105 > 105 24 hours > 105 0 > 105 > 105 > 105 > 105 Table 5 ATCC 29212 Enterococcus faecal is Colony number control group Shihuang Qianyin Commercial SSN 0SN MSN 0 minutes > 105 > 105 > 105 > 105 > 105 > 105 8 hours > 105 0 > 105 > 105 > 105 > 105 24 hours > 105 0 > 105 > 105 > 105 > 105

1919

200831117 表6 __ ATCC 7002 Proteus mirabilis^^落备 對照組 石黃在安銀 0分鐘 > 105 > 105 8小時 > 105 0 24小時 > 105 0 表7 ATCC 19606 Acinetobacter 對照組 石黃在安銀 市售品 0分鐘 > 105 > 105 > 105 8小時 > 105 0 > 105 24小時 > 105 0 > 105 ® 表8烫傷後第31天評分200831117 Table 6 __ ATCC 7002 Proteus mirabilis ^^ falling control group Shihuang in An Yin 0 minutes > 105 > 105 8 hours > 105 0 24 hours > 105 0 Table 7 ATCC 19606 Acinetobacter control group Shihuang in An Yin 0 minutes > 105 > 105 > 105 8 hours > 105 0 > 105 24 hours > 105 0 > 105 ® Table 8 Rating on the 31st day after burn

第31天 對照組 Silver sulfadiazine 1% cream 市售 紫雲膏 麻、; T奈米微 —是膠 —---- 撖欖油紫 雲膏奈; 微句凝膠 礦物油紫 雲膏奈米 撒句凝f蓼 A兔 2 2 1 2 2 2 B兔 1 3 2 2 9 9 Η兔 1 3 2 —-------- 2 L 5 L 2 J兔 2 2 2 4 5 2 Κ兔 2 2 2 4 5 5 L兔 2 2 2 4 2 2 總計 10 14 12 -------- 18 23 15 平均 1· 67土0. 52 2. 33±0. 52 2±0 2. 83+1. 33 3.50±1.64 2. 50±1. 22 20 200831117On the 31st day, the control group Silver sulfadiazine 1% cream commercially available Ziyun cream hemp; T nano-micro- is glue----- 撖油油紫云膏奈; 句句凝胶矿物油紫云膏奈米撒句凝蓼A rabbit 2 2 1 2 2 2 B rabbit 1 3 2 2 9 9 Η rabbit 1 3 2 —-------- 2 L 5 L 2 J rabbit 2 2 2 4 5 2 Κ rabbit 2 2 2 4 5 5 L rabbit 2 2 2 4 2 2 Total 10 14 12 -------- 18 23 15 Average 1.67 soil 0. 52 2. 33±0. 52 2±0 2. 83+1. 33 3.50±1.64 2. 50±1. 22 20 200831117

第37天 對照組 Silver sulfadiazine 1% creamDay 37 Control Silver sulfadiazine 1% cream

麻油紫雲 貧奈米微 膠 橄欖油紫 雲膏奈米 微包凝膠 礦物油紫 雲膏奈米 微包凝膠 4 5 2 3 5 4 5 5 5 5 5 4 26 26 4. 33±1.21 4. 33±0. 81 摩_10纾!量表總表Sesame oil purple cloud lean nano micro-gel olive oil purple cloud cream nano micro-encapsulated gel mineral oil purple cloud cream nano micro-package gel 4 5 2 3 5 4 5 5 5 5 5 4 26 26 4. 33±1.21 4. 33± 0. 81 _10 纾! Scale summary

敷料1:對照組敷 敷料4:麻峨㈣微包凝膠娜··橄欖油物奈米微包凝膠 敷料6 ·礦物油紫S膏奈米微包_。 21 200831117Dressing 1: Control group dressing 4: paralysis (4) micro-package gel Na · olive oil nano-package gel dressing 6 · mineral oil purple S cream nano-package _. 21 200831117

s J„ )H<LO姝啭¥叙^翱齡韧螺 s J„ ) <9 姝 總分 CO LO CO OO 膠原組織生長程度 Κ- -Μ Μ -¾ 埘姐_噼费斗 鉍_ 2刼鲶讀Η 句刼漂Η鉍咚_命 .· _ gΘ鲶甸斗 ^ S W K- <°^ Η 野i 婵每哨奚 v^ K \<r W. • * · · « · · > i <N1 —邮 CD 啤 <ZD r-H T-H τ—Η οα 1 ( C<1 1—H 03 oo 新生血管增生程度 你 s \^/ t-H C3> CD CD CD 7—1 璀 c 纖維母細胞增生程度 枇 s CD 〇 ο CD CD T1·' t 平滑肌 杷 s τ—1 t—H CD τ--Η CD r—H 大汗腺 椒 s C3> CD CD CD 〇) 〇> 毛囊 杷 s r—H r—H r—Η τ—H r—H f t 墀 二 表皮增生程度 杷 s t—H r—4 τ—4 t-H τ—H r-H 墀 Q 表皮過度角化程度 杯 s r—I t-H τ—Η r _H τ—H r—H 碱 Q 評分 項目 敷料1 敷料2 敷料3 敷料4 敷料5 敷料6 给鎵初¾来你4_鉍谀荽襻:9实鉍。#嫁初«呆.如_鉍谀韜«:1-0实鵪 。s窫呆你如#鉍号_ : 。如S鉍雜柃:coisl。w«¥:2*^。崩恶 ττ 200831117 【圖式簡單說明】 第一圖:為紫雲膏奈米微包液粒徑分析線圖; 第二圖(A):為Pseudomonas aeruginosa菌分別於對照組 (a)、磺銨銀組(b)及市售品組(c)各培養0、8及24小時候 菌落圖; 第二圖(B):為 Pseudomonas aeruginosa 菌分別於 SSN 組 (d)、0SN組(e)及MSN組(f)各培養0、8及24小時候菌落圖; • 第三圖:為兔子烫傷後第31天對照組(a)、磺銨銀組(b)、 市售品組(c)、SSN組(d)、0SN組(e)及MSN組(f)傷口外 觀圖(虛線圓框為原始燙傷面積); 第四圖:為兔子燙傷後第37天對照組(a)、磺銨銀組(b)、 市售品組(c)、SSN組(d)、0SN組(e)及MSN組(f)傷口外 觀圖(虛線圓框為原始燙傷面積);以及 第五圖(A) -(F):分別為燒燙傷後第20天對照組、磺銨 銀組、市售品組、SSN組、0SN組及MSN組於光學倍數20 ⑩ 倍下傷口組織的Η & E染色圖。 【主要元件符號說明】 無 23s J„ )H<LO姝啭¥叙^翱龄韧螺 s J„ ) <9 姝 total score CO LO CO OO Collagen tissue growth degree Κ - -Μ Μ -3⁄4 埘姐_噼费斗铋_ 2刼鲶 Η 刼 刼 刼 命 命 命 命 SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW SW > i <N1 - Mail CD Beer <ZD rH TH τ-Η οα 1 ( C<1 1—H 03 oo Neovascular proliferation degree s \^/ tH C3> CD CD CD 7-1 璀c fiber The degree of blast proliferation 枇s CD 〇ο CD CD T1·' t smooth muscle 杷 s τ-1 t-H CD τ--Η CD r-H apocalyptic s C3> CD CD CD 〇) 〇> hair follicle 杷r —H r—H r—Η τ—H r—H ft 墀Second epidermal hyperplasia 杷st—H r—4 τ—4 tH τ—H rH 墀Q Epidermal hyperkeratosis degree cup sr—I tH τ—Η r _H τ—H r—H alkali Q score item dressing 1 dressing 2 dressing 3 dressing 4 dressing 5 dressing 6 to gallium first 3⁄4 come to you 4_铋谀荽襻:9 real. #嫁初«呆. Such as _铋谀韬«: 1-0 real 鹌. s 窫 你 you like #铋号_ : . Such as S 铋 柃: coisl. w«¥:2*^. Disintegration ττ 200831117 [Simple description of the diagram] The first picture: the particle size analysis line of the Ziyun cream nano-package liquid; The second picture (A): Pseudomonas aeruginosa bacteria in the control group (a), sulfonium silver Group (b) and commercial group (c) were colonized at 0, 8 and 24 hours in each culture; Figure 2 (B): Pseudomonas aeruginosa in SSN group (d), 0SN group (e) and MSN group (f) Colony maps at 0, 8 and 24 hours of culture; • Figure 3: Control group (a), sulfonium silver group (b), commercial group (c), SSN on day 31 after burn injury in rabbits Group (d), 0SN group (e) and MSN group (f) Appearance of the wound (the dotted circle is the original burned area); The fourth picture: the control group (a), the sulfonium silver group on the 37th day after the burn (b), commercial group (c), SSN group (d), 0SN group (e) and MSN group (f) appearance of the wound (the dotted circular frame is the original burned area); and the fifth figure (A) - (F): Η & E staining of the wound tissue at the optical multiple of 20 10 times in the control group, the sulfonium silver group, the commercial product group, the SSN group, the 0SN group and the MSN group on the 20th day after the burn. [Main component symbol description] None 23

Claims (1)

200831117 十、申請專利範圍: 1. 一種治療皮膚病之奈米微包液,含有下列成分: 一油性基質; 一紫草萃取液,係將一紫草經由該油性基質萃取過 濾而得;以及 一當歸萃取液,係將一當歸經由該油性基質萃取過 濾而得,其中該油性基質、該紫草萃取液及該當歸萃取 液係包覆於一填脂質(phospholipids)層内,形成粒徑 小於100奈米之一奈米微包。200831117 X. Patent application scope: 1. A nano-package solution for treating skin diseases, comprising the following components: an oily substrate; a comfrey extract obtained by extracting and filtering a comfrey through the oily substrate; The extract of Angelica sinensis is obtained by extracting and filtering the Angelica sinensis via the oily substrate, wherein the oily substrate, the comfrey extract and the extract of Angelica sinensis are coated in a layer of phospholipids to form a particle size of less than 100. One of the nano-micro packets of nano. 2·如申請專利範圍第1項之奈米微包液,其中該油性基質 包含麻油、礦物油及撖欖油之至少其中之一。 3·如申請專利範圍第1項之奈米微包液,其中該奈米微包 外更包覆一水層。 4·如申請專利範圍第1項之奈米微包液,其中該磷脂質層 係由甘油及石粦脂質所組成。 5·=申請專利範圍第1項之奈米微包液,其中該皮膚病包 t ^跌打損傷、擦傷、刀傷、燒燙傷、皮膚乾燥、皸裂、 >貝瘍、束傷及增殖性皮膚異常。 •種冶療皮膚病之奈米微包凝膠,其含有下列成分: 一油性基質; 一紫草萃取液,係將一紫草經由該油性基質萃取過 履而得; 作;s歸萃取液,係將一當歸經由該油性基質萃取過 /愿而得;以及 歸萃油性基質、該紫草萃取液及該當 成轮丨认夂後;一石辞脂質(ph〇sph〇iipids)層内,形 成粒徑小於100奈米之一奈米微包。 6項之奈米微包凝膠,其巾該賦形劑 馬喊%和一親水性軟膏其中之一。 24 200831117 8· ί申請專利範圍第6項之奈米微包凝膠,其中該油性基 質包含麻油、礦物油及撖欖油之至少其中之_。 9.如申請專利範圍第6項之奈米微包凝/膠,其中該奈米微 包外更包覆一水層。 10·如申^青專利範圍第6項之奈米微包凝膠,其中該磷脂 貝層係由甘油及石粦脂質所組成。 11括種製備治療皮膚病之奈米微包液的方法,其步驟包 (a)利用了油性基質萃取-紫草與-當歸以得到-萃 取液, ⑻入一磷脂質及水,高速高壓攪拌 使该卒取液均質化;以及 (C)過濾該萃取液。 12中如牛申J項之製備奈米微包液的方法4 甲步驟(a)之丽更包括一步 丄 該油性基質中2 4小時。 *歸於至溫下先浸泡於 13·如申請專利範圍第u項 ' 中步驟(a)中更包括一步驟:匕液的方法,其 13G〜14G度以萃取該紫草及該當^將㈣性物質加熱至 14·如申請專利範圍第n項之— 中步驟⑹係使㈣徑包液的方法’其 15·如申料職圍们丨項 中步驟(a )之該油性基質包含m f包液的方法’其 少其中之一。 、匕3屣油、礦物油及橄欖油之至 16·如申請專利範圍第 中步驟(c)之後更包含一步驟示米微包液的方法,其 该萃取液並混和攪拌。 ϋ入賦形劑於過濾後的 17·如申請專利範圍第17項之太、 中該賦形劑為一凝膠及一 ^ = f彳政包液的方法·,其 親水性軟貪其中之一。 25 200831117 七、指定代表圖: (一) 本案指定代表圖為:第()圖。 (二) 本代表圖之元件符號簡單說明: 無 八、本案若有化學式時,請揭示最能顯示發明特徵的化學式:2. The nanocapsule according to item 1 of the patent application, wherein the oily base comprises at least one of sesame oil, mineral oil and eucalyptus oil. 3. The nano-package liquid of claim 1 of the patent scope, wherein the nano-package is further coated with an aqueous layer. 4. The nanocapsule according to item 1 of the patent application, wherein the phospholipid layer is composed of glycerin and sarcophagus lipid. 5·=Application of the nanometer microencapsulation liquid of the first paragraph of the patent scope, wherein the skin disease package t ^ bruises, abrasions, knife wounds, burns, dry skin, chapped, > shell, neck, and proliferative Abnormal skin. a nano-package gel for treating skin diseases, which comprises the following components: an oily substrate; a comfrey extract obtained by extracting a comfrey through the oily substrate; , which is obtained by extracting an angelica via the oily substrate; and extracting the oily substrate, the comfrey extract and the rim of the stalk; and forming a layer of ph〇sph〇iipids One nanometer micro-package with a particle size of less than 100 nm. 6 items of nano-package gel, the towel of which is one of the excipients of the horse shouting % and a hydrophilic ointment. 24 200831117 8· ί. The nano-package gel of claim 6 wherein the oily base comprises at least one of sesame oil, mineral oil and eucalyptus oil. 9. The nano-microgel/gel according to item 6 of the patent application, wherein the nano-pack is coated with an aqueous layer. 10. The nano-microgel gel of claim 6, wherein the phospholipid shell layer is composed of glycerin and sarcophagus lipid. 11 is a method for preparing a nano-encapsulated liquid for treating skin diseases, wherein the step (a) utilizes oily matrix extraction - comfrey and - angelica to obtain - extract, (8) into a phospholipid and water, high speed and high pressure stirring The draw liquid is homogenized; and (C) the extract is filtered. In the method of preparing the nano-encapsulation liquid in the case of Niu Shen J, the step A (a) further includes a step of 2 in the oily substrate for 24 hours. *Because the temperature is first immersed in 13 · As in the scope of application patent section u ', step (a) further includes a step: sputum method, 13G ~ 14G degrees to extract the comfrey and the ^ ^ (four) sex The substance is heated to 14 · as in the scope of the application of the nth item - (6) is the method of making (4) the diameter of the liquid encapsulation 'the 15', the oily substrate containing the mf encapsulation in the step (a) of the application The method 'its one of them less. , 匕 3 屣 oil, mineral oil and olive oil to 16 · If the step (c) of the patent application scope further comprises a step of the rice micro-encapsulation method, the extract is mixed and stirred. Incorporating the excipient into the filtered 17· as in the scope of claim 17 of the patent, the excipient is a gel and a method of ^ ^ f彳 political encapsulation, and its hydrophilic soft greed One. 25 200831117 VII. Designated representative map: (1) The representative representative of the case is: (). (2) A brief description of the symbol of the representative figure: None 8. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention:
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TWI480061B (en) * 2011-09-29 2015-04-11
WO2022227321A1 (en) * 2021-04-27 2022-11-03 振德医疗用品股份有限公司 Corrosion-resistant stoma leakage-proof paste capable of achieving self-regulation of strength and preparation method therefor

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